How cells coordinate to form mechanically stable, functional three dimensional tissues and organisms is arguably the most interesting and important problem in 21st century biological sciences. It underlies not just normal development and physiology but also cancer and heart disease, the major killers in developed nations. Our lab studies two critical and related aspects of these problems. They are: integrin signaling, or how cells respond to extracellular matrix; and mechanotransduction, or how cells respond to mechanical forces. We study both fundamental aspects of these processes and their roles in the vascular system, particularly atherosclerosis and other vascular diseases. More broadly, we aim to relate our basic discoveries in cell biology to human disease its treatment. Thus, as befits a basic scientist in the Yale Department of Medicine, our research program brings together tools and approaches from cell biology, biophysics and bioengineering with developmental systems and models of human disease.
Talin tension TIRF time lapse.
Using the tension sensor technology developed in our lab (see Grashoff, 2010 Nature), we developed a sensor for mechanical tension across the focal adhesion protein talin that links integrins to the actin cytoskeleton (see Kumar 2016 J. Cell Biol.). Imaging was done using total internal reflection (TIRF) optics. Frames taken from a movie show talin FRET ratio (FRET emission/acceptor intensity) demonstrating gradients of tension withing single focal adhesions, adhesion formation, sliding and disassembly.